Feasibility and Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation for Insomnia in Survivors of Childhood Acute Lymphoblastic Leukemia
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 40
- 试验地点
- 1
- 主要终点
- Mean Change in Subjective Sleep Quality
研究概览
简要总结
This pilot study will assess the usefulness and potential effectiveness of using transcutaneous auricular vagus nerve stimulation (tVNS) for treating insomnia in adult survivors of childhood acute lymphoblastic leukemia (ALL). Participants will be randomized to receive either active (verum) or inactive (sham) nightly stimulation using a non-invasive earbud device over two time periods: 2 weeks and 8 weeks. The study will assess adherence to the intervention and estimate its effects on sleep quality, stress, and neurocognitive function.
Primary Objective:
Aim 1: To determine a) short-term and b) long-term feasibility of tVNS in terms of participation in ALL Survivors with moderate to severe insomnia.
Aim 2: To estimate the effect size of tVNS on sleep quality, stress, and neurocognitive outcomes in ALL survivors with insomnia.
Exploratory Objectives
Aim 1: To investigate the onset of tVNS effect via actigraphy measures over the intervention epoch.
Aim 2: To estimate the effect size of genetic variants on sleep quality within verum tVNS.
详细描述
Approximately 40 adult survivors of childhood ALL enrolled in the SJLIFE cohort will be recruited. Eligible participants must have moderate to severe insomnia (ISI ≥8). The intervention involves nightly use of a tVNS device for 20 minutes before sleep. Participants will be randomized to receive either active or sham stimulation. Feasibility will be assessed based on adherence rates, and efficacy will be estimated using subjective (PSQI, ISI) and objective (actigraphy, CNS Vital Signs) measures. Exploratory analyses will examine the onset of tVNS effects and the influence of genetic variants (BDNF rs6265, COMT rs4680) on treatment response.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Device Feasibility
- 盲法
- Single (Participant)
盲法说明
The participant will be blinded to the assigned treatment.
入排标准
- 年龄范围
- 20 Years 至 50 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Survivor of Acute Lymphoblastic Leukemia (ALL)
- •Enrolled on SJLIFE
- •Participant was less than 21 years of age at time of diagnosis.
- •Age 20-50 years at the time of enrollment
- •Insomnia Severity Index >=8 (Proxy >=8) confirmed prior to enrollment
- •Access to home Wi-Fi and Smartphone
- •Participant is able to speak and understand the English language
- •Participant is able and willing to give consent
排除标准
- •Unable to understand the details and requirements of the study (at the discretion of the PI)
- •Female participants who are pregnant or planning to become pregnant
- •Presence of implanted electrical medical devices (i.e. pacemaker)
- •Currently taking medication intended to treat neurocognitive impairment (i.e. stimulants) or medications prescribed for seizure management
- •History of skin irritation or other issues during stimulation of inner ear
- •Currently utilizing a technological intervention for a sleep disorder (e.g. CPAP)
- •Medications and behavioral practices (white noise, night-time yoga, etc) are acceptable as long as the insomnia is persistent.
- •History of a contraindicated health condition including:
- •Syncope (CTCAE >2)
- •Cardiac dysrhythmia (CTCAE >2)
- •Vascular Disease (CTCAE >2)
- •Coronary Artery Disease (CTCAE >2)
- •Active contraindicated heath condition including:
- •Cranial Nerve Disorder (CTCAE >2)
- •Cardiac tachycardia (CTCAE >2)
- •Neuropathy (Cranial Nerves) (CTCAE >2)
- •Neuralgia (Cranial Nerves) (CTCAE >2)
- •Overt Cerebrovascular Accident (CTCAE >2)
- •Seizures (Any in most recent 1 year
- •Currently enrolled or participating in any other neurostimulation or neuromodulation ancillary research studies
研究组 & 干预措施
Verum tVNS (Active Treatment)
Participants randomized to receive active transcutaneous auricular vagus nerve stimulation (tVNS) using the Soterix device. Stimulation is delivered nightly for 20 minutes at 80% of the participant's discomfort threshold.
干预措施: Soterix tVNS device (Device)
Verum tVNS (Active Treatment)
Participants randomized to receive active transcutaneous auricular vagus nerve stimulation (tVNS) using the Soterix device. Stimulation is delivered nightly for 20 minutes at 80% of the participant's discomfort threshold.
干预措施: Sleep Quality (Behavioral)
Verum tVNS (Active Treatment)
Participants randomized to receive active transcutaneous auricular vagus nerve stimulation (tVNS) using the Soterix device. Stimulation is delivered nightly for 20 minutes at 80% of the participant's discomfort threshold.
干预措施: Neurocognitive and mental health outcomes (Behavioral)
Sham tVNS (Placebo Comparator)
Participants randomized to receive sham stimulation using the same Soterix device, but with no active electrical stimulation. The procedure mimics the verum condition in duration and setup.
干预措施: Soterix tVNS device (sham programmed) (Device)
Sham tVNS (Placebo Comparator)
Participants randomized to receive sham stimulation using the same Soterix device, but with no active electrical stimulation. The procedure mimics the verum condition in duration and setup.
干预措施: Sleep Quality (Behavioral)
Sham tVNS (Placebo Comparator)
Participants randomized to receive sham stimulation using the same Soterix device, but with no active electrical stimulation. The procedure mimics the verum condition in duration and setup.
干预措施: Neurocognitive and mental health outcomes (Behavioral)
结局指标
主要结局
Mean Change in Subjective Sleep Quality
时间窗: Baseline, 2-weeks, 8-weeks
Pittsburgh Sleep Quality Index (PSQI, 0-57 points). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in clinical insomnia score
时间窗: Baseline, 2-weeks, 8-weeks
Insomnia Severity Index (ISI, 0-28 points). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Occurrence of side effects
时间窗: Week 1, Week 2, Week 3, Week 4, Week 5, Week 6, Week 7
Patient Report of Incidence of Side Effects (PRISE). Descriptive statistics of the change between baseline and 2 and 8 weeks will be reported.
Adherence to intervention
时间窗: 2-weeks, 8-weeks
Number of tVNS sessions performed. Descriptive statistics of adherence at 2 weeks and 8 weeks will be reported.
Mean change in Processing Speed (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Symbol Digit Coding Test as the difference between correct responses and errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Executive Function (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Shifting Attention Task as the difference between correct responses and errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Simple Attention (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Continuous Performance Test as the difference between correct responses and commission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Reaction Time (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Stroop Test as the average of reaction times in the complex and default trials. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Sustained Attention (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Four-Part Continuous Performance Test as the difference between correct responses and incorrect responses in Part 2, 3, and 4. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Working Memory (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Four-Part Continuous Performance Test as the difference between correct responses and incorrect responses in Part 4 only. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Complex Attention (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Evaluated with the Stroop Test (ST), Shifting Attention Test (SAT), and Continuous Performance Test (CPT) as the sum of ST commission errors, SAT errors, CPT commission errors, and CPT omission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Cognitive Flexibility (age adjusted z-score)
时间窗: Baseline, 2-Weeks, 8-weeks
Evaluated with the Stroop Test (ST) and Shifting Attention Test (SAT) as the difference between SAT correct responses and the sum of the SAT errors and ST commission errors. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean change in Depression, Anxiety, and Stress (scales)
时间窗: Baseline, 2-Weeks, 8-weeks
Evaluated with Depression Anxiety Stress Scale Short Form (DASS SF-21). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported. DASS SF-21 are reported as population z-scores and categorized into five severity ranges: normal, mild, moderately severe, and extremely severe. The severity levels, higher percentiles being more severe, are determined by z-scores from the DASS manual.
Mean Change in Heart Rate Variability (ms)
时间窗: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Root Mean Square Successive Difference (RMSSD) of heart rate variability. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean Change in Sleep Onset Latency (minutes)
时间窗: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Sleep Onset Latency (time in bed before sleep). Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
Mean Change in Waking Events (count)
时间窗: Weekly means of daily measurements at baseline, at 2-weeks, and at 8-weeks
Number of Awakenings. Descriptive statistics of the difference between experiment arms of the change between baseline and 2 weeks, and baseline and 8 weeks will be reported.
次要结局
未报告次要终点